Experiences with human patients and long-term experiments in laboratory rats show that some metal alloys, commonly used in implant surgery, may responsible for the development of implant site tumors. Our preliminary studies suggested that the risk of such tumor development might be attributed to (1) high nickel, cobalt, or chromium contents in the implants; and (2) large implant surface areas, typical of cementless porous sintered devices. Since our experiments were done with porous sintered implants, which had surface areas to host body weight ratios that were significantly lower than those experienced by human, who underwent a total hip replacement with a cementless, porous sintered device, we do not know the true carcinogenic risk, to which human with porous sintered devices are subjected, and the critical surface to body weight ratios for the development of implant site cancers. In this application, we propose to evaluate in a long-term experiment in laboratory rats, the carcinogenic risk of porous sintered CoCr-Mo devices of various surface areas. Devices of two different implant surface area to host body weight ratios will be implanted into rat femoral bones. The first ratio will be similar to that of a porous sintered device replacing the human hip, the second ratio will be 100 times that value. Metal surface area per unit body weight and tumor incidence will be compared with the accumulation of metal ions in surrounding and remote tissues. In order to account for lesions that may develop in response to the relatively large implant size, we shall compare experimental groups with a control group which will harbour solid implants of the of same size and shape as those in the experimental groups. In addition, this proposal introduces a novel in vitro screening assay for the carcinogenesis testing of metal devices. In this assay, we shall grow fetal Syrian hamster fibroblasts for several passages on collagen-coated, porous sintered metal alloys. After each passage, a cell sample will be analyzed for the presence of transformed mutants, using a standard colony-forming assay. These studies will help us to establish baseline risk factors for human patients and will allow us to prescreen new metal devices for their biological suitability in human implant surgery.